Blood and Marrow Transplant Clinical Trials Network Report on the Development of Novel Endpoints and Selection of Promising Approaches for Graft-versus-Host Disease Prevention Trials

• Published in: Biology of blood and marrow transplantation 2018-06, Vol.24 (6), p.1274-1280
• Main Authors: Pasquini, Marcelo C., Logan, Brent, Jones, Richard J., Alousi, Amin M., Appelbaum, Frederick R., Bolaños-Meade, Javier, Flowers, Mary E.D., Giralt, Sergio, Horowitz, Mary M., Jacobsohn, David, Koreth, John, Levine, John E., Luznik, Leo, Maziarz, Richard, Mendizabal, Adam, Pavletic, Steven, Perales, Miguel-Angel, Porter, David, Reshef, Ran, Weisdorf, Daniel, Antin, Joseph H.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Biomarkers; Clinical Protocols; Clinical trials; Clinical Trials as Topic - methods; Databases, Factual; Disease-Free Survival; Female; Graft vs Host Disease - prevention & control; GVHD; Hematopoietic cell transplantation; Hematopoietic Stem Cell Transplantation - adverse effects; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic Stem Cell Transplantation - mortality; Humans; Male; Middle Aged; Recurrence; Treatment Outcome; Young Adult
• ISSN: 1083-8791; 1523-6536
• DOI: 10.1016/j.bbmt.2018.01.002

•An approach to use an outcomes database to compare single-center phase II data is proposed.•Testing six different GVHD prophylaxis regimens against a common control resulted in the identification of promising interventions for further study in multicenter clinical trials.•Use of composite endpoints that consider GVHD, relapse, and death increase the efficiency of clinical trial design of GVHD prevention interventions.•GRFS, CRFS, and IRFS are proposed novel endpoints for studying GVHD prophylaxis approaches. Graft-versus-host disease (GVHD) is a common complication after hematopoietic cell transplantation (HCT) and associated with significant morbidity and mortality. Preventing GVHD without chronic therapy or increasing relapse is a desired goal. Here we report a benchmark analysis to evaluate the performance of 6 GVHD prevention strategies tested at single institutions compared with a large multicenter outcomes database as a control. Each intervention was compared with the control for the incidence of acute and chronic GVHD and overall survival and against novel composite endpoints: acute and chronic GVHD, relapse-free survival (GRFS), and chronic GVHD, relapse-free survival (CRFS). Modeling GRFS and CRFS using the benchmark analysis further informed the design of 2 clinical trials testing GVHD prophylaxis interventions. This study demonstrates the potential benefit of using an outcomes database to select promising interventions for multicenter clinical trials and proposes novel composite endpoints for use in GVHD prevention trials.